Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120)

NCT01595646 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00023230ZEN-10-173646US
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

The study will examine the effects of intranasally administered long-acting insulin detemir on cognition in persons with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI). The rationale for these studies is derived from growing evidence that insulin contributes to multiple brain functions, and that insulin dysregulation can contribute to AD pathogenesis. Thus, therapies aimed at restoring normal insulin signaling in the CNS may have beneficial effects on brain function. Intranasal administration of insulin increases insulin signaling in the brain without raising peripheral levels and causing hypoglycemia. Insulin detemir is an insulin analogue that may have better action in brain than other insulin formulations because of its albumin binding properties. The investigators will test the therapeutic effects of intranasally-administered insulin detemir in a study in which participants will receive insulin detemir, regular insulin, or placebo over a four month period. The investigators will test the hypothesis that insulin and insulin detemir will both improve memory and daily functioning in persons with AD/aMCI compared with placebo, but that insulin detemir will have the greatest effect.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Keywords

Memory; Intranasal insulin; Alzheimer's disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Verbal Memory Composite

  The composite will consist of the sum of Z scores for Delayed Story Recall and Buschke Selective Reminding Test. In the Story Recall test subjects listen to a story containing 44 informational bits that is read once. Subjects will be asked to recall the story immediately after the reading and after a 20-min delay. Credit is awarded for each bit recalled verbatim or accurately paraphrased. The Buschke Selective Reminding Test measures verbal memory through multiple trials of a list learning task. A list of 12 words is audibly presented to the subject, and subjects recall as many words as possible. On subsequent trials, subjects are only told those words they omitted on the previous trial. The procedure continues until the subject recalls all words on two successive trials or to the twelfth trial. After a 30-minute delay, subjects recall as many items as possible. Number of items recalled after the delay will be summed. Higher scores indicate better performance.

  Change from Baseline in Verbal Memory at 16 weeks

Secondary Outcomes (4)

• Cerebral Spinal Fluid (CSF) Biomarkers of AD

  Change from Baseline in CSF Biomarkers at 16 Weeks

• Cerebral Spinal Fluid (CSF) Biomarkers of AD TTau-P181/Abeta42 Ratio

  Change from Baseline in CSF Biomarkers at 16 Weeks

• Functional Ability

  baseline, month 2, and month 4

• The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI Revision

  Baseline, Month 2 and Month 4

Other Outcomes (4)

• Executive Function Composite

  Change from Baseline in Executive Functioning at 16 Weeks

• Plasma Biomarkers of AD

  Change from Baseline in Plasma Biomarkers at 16 Weeks

• Cerebral Blood Flow

  Change from Baseline in Cerebral Blood Flow at 16 Weeks

Study Arms (3)

Saline

PLACEBO COMPARATOR

Saline placebo taken twice per day via intranasal route.

Drug: Saline

Insulin Detemir

EXPERIMENTAL

20IU of Insulin Detemir taken twice per day (40IU total per day) via intranasal route

Drug: Insulin detemir

Insulin

EXPERIMENTAL

20IU Insulin, administered twice per day (40IU total per day) via intranasal route

Drug: Insulin

Interventions

Saline DRUG

Saline, administered intranasally twice per day for a 16 week duration

Also known as: Saline solution

Saline

Insulin detemir DRUG

20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)

Also known as: Levemir

Insulin Detemir

Insulin DRUG

20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)

Also known as: Novolin R

Insulin

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50-89
• Diagnosed with mild cognitive impairment, or mild/moderate AD

You may not qualify if:

• Excessively high or low blood pressure, heart rate
• Pre-existing diabetes not controlled by exercise/diet
• Previous/current use of insulin
• Significant elevations in lipids, liver enzymes
• Menstrual period within the last 12 months
• Significant neurological or medical disorder (other than AD)
• Significant use of nasal decongestants
• Current use of anti-psychotic, anti-convulsive, anxiolytic, glucocorticoids, or sedative medications

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Alzheimer's Association: collaborator

Study Sites (2)

Wake Forest Baptist Hospital

Winston-Salem, North Carolina, 27157, United States

Location

VA Puget Sound Health Care System - American Lake Division

Tacoma, Washington, 98493, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Sodium Chloride; Saline Solution; Insulin Detemir; Insulin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proinsulin

Results Point of Contact

• Title: Suzanne Craft, PhD
• Organization: Wake Forest School of Medicine

suzcraft@wakehealth.edu

3366-713-8830

Study Officials

• Suzanne Craft, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Study Start: November 1, 2011
• Primary Completion: March 12, 2015
• Study Completion: March 12, 2015
• Last Updated: November 17, 2020
• Results First Posted: February 1, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)